1. N-acetylcysteine delayed cadmium-induced chronic kidney injury by activating the sirtuin 1–P53 signaling pathway
- Author
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Wenxuan, Dong, Kanglei, Zhang, Zhonggui, Gong, Tongwang, Luo, Jiahui, Li, Xueru, Wang, Hui, Zou, Ruilong, Song, Jiaqiao, Zhu, Yonggang, Ma, Gang, Liu, and Zongping, Liu
- Subjects
General Medicine ,Toxicology - Abstract
With the development of modern industrial civilization, cadmium (Cd), a known nephrotoxic metal, has become a growing public safety issue due to its ability to induce various types of kidney disease. Maladaptive proximal tubule repair is a significant cause of Cd-induced chronic kidney disease (CKD), which is characterized by premature senescence and pro-fibrosis. Previously, we demonstrated that cadmium causes DNA damage and cycle arrest in renal tubular epithelial cells, which may be relevant to premature senescence regulated by sirtuin 1 (SIRT1). In this study, in vivo and in vitro studies were conducted to elucidate the role of SIRT1-mediated premature renal senescence in Cd-induced CKD. As oxidative stress is a significant cause of aging, we evaluated whether N-acetylcysteine (NAC) would inhibit Cd-induced premature aging and dysfunction in rat renal tubular epithelial cells. Cadmium induced premature renal senescence and fibrosis, and NAC inhibited premature renal senescence and fibrosis through the SIRT1-P53 pathway and delayed CKD progression. Overall, the results suggested that the SIRT1-P53 pathway mediates oxidative stress, premature renal senescence, and renal fibrosis during cadmium exposure, which may be a potential therapeutic target for Cd-induced CKD.
- Published
- 2023
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